Altered kidney CYP2C and cyclooxygenase-2 levels are associated with obesity-related albuminuria

Aparajita Dey, Roger S. Williams, David M. Pollock, David W. Stepp, John W. Newman, Bruce D. Hammock, John D. Imig

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Objective: To determine cytochrome P450 (CYP450) and cyclooxygenase (COX) expression and metabolite regulation and renal damage in the early stages of obesity-related hypertension and diabetes. Research Methods and Procedures: Obese and lean Zucker rats at 10 to 12 weeks of age were studied. Blood pressure was measured in the conscious state using radiotelemetry. Blood glucose levels and body weight were measured periodically. Protein expression of CYP450 and COX enzymes in the kidney cortex, renal microvessels, and glomeruli was studied. The levels of CYP450 and COX metabolites in urine were measured, and urinary albumin excretion, an indicator of kidney damage, was measured. Results: Body weight and blood glucose averaged 432 ± 20 grams and 105 ± 5 mg/dl, respectively, in obese Zucker rats as compared with 320 ± 8 grams and 91 ± 5 mg/dl, respectively, in age-matched 10- to 12-week-old lean Zucker rats. Renal microvascular CYP4A and COX-2 protein levels were increased 2.3- and 17.0-fold, respectively, in obese Zucker rats. The protein expression of CYP2C11 and CYP2C23 was decreased 2.0-fold in renal microvessels isolated from obese Zucker rats when compared with lean Zucker rats. The urinary excretion rate of thromboxane B2 was increased significantly in obese Zucker as compared with lean Zucker rats (22.0 ± 1.8 vs. 13.4 ± 1.0 ng/d). Urinary albumin excretion, an index of kidney damage, was increased in the obese Zucker rat at this early age. Discussion: These results suggest that increased CYP4A and COX-2 protein levels and decreased CYP2C11 and CYP2C23 protein levels occur in association with microalbuminuria during the onset of obesity-related hypertension and type 2 diabetes.

Original languageEnglish (US)
Pages (from-to)1278-1289
Number of pages12
JournalObesity Research
Volume12
Issue number8
StatePublished - 2004

Fingerprint

Zucker Rats
Albuminuria
prostaglandin synthase
Cyclooxygenase 2
obesity
Obesity
kidneys
Kidney
rats
Cytochrome P-450 Enzyme System
Prostaglandin-Endoperoxide Synthases
Cytochrome P-450 CYP4A
cytochrome P-450
excretion
Microvessels
Proteins
blood glucose
hypertension
albumins
Blood Glucose

Keywords

  • Epoxyeicosatrienoic acids
  • Nephropathy
  • Obese Zucker rats
  • Prostaglandins
  • Type 2 diabetes

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Public Health, Environmental and Occupational Health
  • Endocrinology
  • Food Science
  • Endocrinology, Diabetes and Metabolism

Cite this

Dey, A., Williams, R. S., Pollock, D. M., Stepp, D. W., Newman, J. W., Hammock, B. D., & Imig, J. D. (2004). Altered kidney CYP2C and cyclooxygenase-2 levels are associated with obesity-related albuminuria. Obesity Research, 12(8), 1278-1289.

Altered kidney CYP2C and cyclooxygenase-2 levels are associated with obesity-related albuminuria. / Dey, Aparajita; Williams, Roger S.; Pollock, David M.; Stepp, David W.; Newman, John W.; Hammock, Bruce D.; Imig, John D.

In: Obesity Research, Vol. 12, No. 8, 2004, p. 1278-1289.

Research output: Contribution to journalArticle

Dey, A, Williams, RS, Pollock, DM, Stepp, DW, Newman, JW, Hammock, BD & Imig, JD 2004, 'Altered kidney CYP2C and cyclooxygenase-2 levels are associated with obesity-related albuminuria', Obesity Research, vol. 12, no. 8, pp. 1278-1289.
Dey A, Williams RS, Pollock DM, Stepp DW, Newman JW, Hammock BD et al. Altered kidney CYP2C and cyclooxygenase-2 levels are associated with obesity-related albuminuria. Obesity Research. 2004;12(8):1278-1289.
Dey, Aparajita ; Williams, Roger S. ; Pollock, David M. ; Stepp, David W. ; Newman, John W. ; Hammock, Bruce D. ; Imig, John D. / Altered kidney CYP2C and cyclooxygenase-2 levels are associated with obesity-related albuminuria. In: Obesity Research. 2004 ; Vol. 12, No. 8. pp. 1278-1289.
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abstract = "Objective: To determine cytochrome P450 (CYP450) and cyclooxygenase (COX) expression and metabolite regulation and renal damage in the early stages of obesity-related hypertension and diabetes. Research Methods and Procedures: Obese and lean Zucker rats at 10 to 12 weeks of age were studied. Blood pressure was measured in the conscious state using radiotelemetry. Blood glucose levels and body weight were measured periodically. Protein expression of CYP450 and COX enzymes in the kidney cortex, renal microvessels, and glomeruli was studied. The levels of CYP450 and COX metabolites in urine were measured, and urinary albumin excretion, an indicator of kidney damage, was measured. Results: Body weight and blood glucose averaged 432 ± 20 grams and 105 ± 5 mg/dl, respectively, in obese Zucker rats as compared with 320 ± 8 grams and 91 ± 5 mg/dl, respectively, in age-matched 10- to 12-week-old lean Zucker rats. Renal microvascular CYP4A and COX-2 protein levels were increased 2.3- and 17.0-fold, respectively, in obese Zucker rats. The protein expression of CYP2C11 and CYP2C23 was decreased 2.0-fold in renal microvessels isolated from obese Zucker rats when compared with lean Zucker rats. The urinary excretion rate of thromboxane B2 was increased significantly in obese Zucker as compared with lean Zucker rats (22.0 ± 1.8 vs. 13.4 ± 1.0 ng/d). Urinary albumin excretion, an index of kidney damage, was increased in the obese Zucker rat at this early age. Discussion: These results suggest that increased CYP4A and COX-2 protein levels and decreased CYP2C11 and CYP2C23 protein levels occur in association with microalbuminuria during the onset of obesity-related hypertension and type 2 diabetes.",
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AU - Dey, Aparajita

AU - Williams, Roger S.

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AU - Newman, John W.

AU - Hammock, Bruce D.

AU - Imig, John D.

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AB - Objective: To determine cytochrome P450 (CYP450) and cyclooxygenase (COX) expression and metabolite regulation and renal damage in the early stages of obesity-related hypertension and diabetes. Research Methods and Procedures: Obese and lean Zucker rats at 10 to 12 weeks of age were studied. Blood pressure was measured in the conscious state using radiotelemetry. Blood glucose levels and body weight were measured periodically. Protein expression of CYP450 and COX enzymes in the kidney cortex, renal microvessels, and glomeruli was studied. The levels of CYP450 and COX metabolites in urine were measured, and urinary albumin excretion, an indicator of kidney damage, was measured. Results: Body weight and blood glucose averaged 432 ± 20 grams and 105 ± 5 mg/dl, respectively, in obese Zucker rats as compared with 320 ± 8 grams and 91 ± 5 mg/dl, respectively, in age-matched 10- to 12-week-old lean Zucker rats. Renal microvascular CYP4A and COX-2 protein levels were increased 2.3- and 17.0-fold, respectively, in obese Zucker rats. The protein expression of CYP2C11 and CYP2C23 was decreased 2.0-fold in renal microvessels isolated from obese Zucker rats when compared with lean Zucker rats. The urinary excretion rate of thromboxane B2 was increased significantly in obese Zucker as compared with lean Zucker rats (22.0 ± 1.8 vs. 13.4 ± 1.0 ng/d). Urinary albumin excretion, an index of kidney damage, was increased in the obese Zucker rat at this early age. Discussion: These results suggest that increased CYP4A and COX-2 protein levels and decreased CYP2C11 and CYP2C23 protein levels occur in association with microalbuminuria during the onset of obesity-related hypertension and type 2 diabetes.

KW - Epoxyeicosatrienoic acids

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KW - Type 2 diabetes

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